Auditory evoked responses during different phases of menstrual cycle

The electrophysiological correlates of changes in sensory function during menstrual cycle has already been studied and attributed to the hormonal influence. Effects of estrogen and progesterone on waves of auditory brainstem responses (ABR) have been reported and a hypothesis has been proposed that sex steroids have more influence on central auditory pathways. As mid-latency responses (MLRs) and slow vertex responses (SVRs) are better indicators of central auditory pathways, so MLRs and SVRs were also recorded besides ABRs in the present study. Waves of ABRs, MLRs & SVRs were recorded in 20 normal cycling females in 4 different phases of menstrual cycles from Cz-A1 and Cz-A2 position with alternating 90dB sound pressure click stimuli. Contralateral ear was masked with a white noise of -40 dBHL. With the same setting by changing the number of click stimuli, intervals of stimuli and filter bandpass the above 3 recordings were taken. The evoked responses in females having ovulatory cycles were compared within the four phases using ANOVA test. There is a trend of increase in peak latencies of ABR waves III and V and IPL I-V in estrogen-peak midcycle while decrease in latencies in progesterone-peak (interpeak latency) midluteal phase. Peak latencies of MLR waves No, Po, Na, Pa and Pb also show a same trend. SVR waves P2 and N2 are significantly delayed in mid-cycle (178.80 +/- 20.49, 276.65 +/- 18.32) while conduction is faster in midluteal phase (166.45 +/- 17.41, 261.95 +/- 21.07). Smallest latencies of all the waves are occurring during menstruation. These findings are suggesting that normal cyclical variations in the levels of estrogen and progesterone during menstrual cycle do affect the auditory pathways and effects are better seen on the central component.     

Marihuana use across the menstrual cycle

Thirty women completed marihuana use diaries and Form T of the Moos Menstrual Distress Questionnaire (MDQ) every day for three consecutive menstrual cycles. A 99.1% response rate was obtained: 2715 of a possible 2741 diaries were returned. Women reported smoking an average of 1.4 (+/- 2.0) marihuana cigarettes per day (range for individuals: 7.3 [+/- 3.8] to 0.2 [+/- 0.4]). There was no significant covariance between daily marihuana smoking and menstrual cycle phase. The psychological MDQ factors reflecting negative affect, difficulty in concentration, behavior change and arousal also did not vary with menstrual cycle phase. The physiological MDQ factors of pain, autonomic reactions and water retention were significantly increased during the premenstrual and/or menstrual phases of the cycle. MDQ scores during the premenstruum and menstruation were generally very low. These data indicate that in the absence of severe premenstrual dysphoria, changes in drug use are not systematically related to phase of the menstrual cycle.     

A study of auditory reaction time in different phases of the normal menstrual cycle

Reaction time is an indirect index of processing capabilities of the central nervous system. The present study was carried out to determine if there is any alteration of simple auditory reaction time across the normal menstrual cycle. In this study, reaction time of 100 female medical and paramedical students was recorded in different phases of their menstrual cycle namely premenstrual, menstrual, middle of proliferative, middle of secretory phase and on the expected day of ovulation. Results were expressed as mean, standard deviation and statistically analyzed using student's paired 't' test. On comparing each phase with the corresponding adjacent phases auditory reaction time was significantly increased (P<0.05) in premenstrual phase and on the expected day of ovulation. Thus fluctuating levels of sex steroids across normal menstrual cycle affect sensory motor association of an individual.     

Effect of different phases of menstrual cycle on physical working capacity in Indian population

Women in large number are engaged in skilled and unskilled sectors of job and there is increasing participation of women in sports, Considering the fact that cyclical endocrine profile in females can have bearing on cardiovascular and respiratory function, in turn on physical capacity, The study of effects of phases of menstrual cycle on physical working capacity was undertaken in 40 female students of Bangalore Medical College. The subjects were instructed to come to the lab during each of three different phases of menstrual cycle. Resting heart rate (HR), respiratory rate (RR), BP were recorded. Subjects were made to exercise on Bicycle Ergometer and their maximum aerobic capacity was assessed as PWC170 (Physical working capacity at the heart rate 170). On statistical analysis we found resting RR and resting HR high during luteal phase with 'P' values of P < 0.01, P < 0.01 respectively. We also found PWC170 decreased during luteal and menstrual phase with 'P' values of P < 0.05 and P < 0.01. From the present study it can be concluded that resting HR and RR are increased during the luteal phase. Also PWC170 is decreased during the luteal and menstrual phases, this can have an adverse effect on the physical work output of females during these two phases.     

Effects of ethanol at four phases of the menstrual cycle

RATIONALE: Ovarian hormones, such as estrogen (E) and progesterone (P), interact with neurotransmitters, such as dopamine and gamma-aminobutyric acid, which are thought to be important in mediating the effects of ethanol. Therefore, it is possible that circulating ovarian hormones influence the acute subjective, behavioral, and physiological effects of ethanol, thus indirectly influencing ethanol consumption. OBJECTIVES: To examine the relationship between hormone levels and consumption of ethanol, this study investigated whether the effects of ethanol and the consumption of ethanol vary as a function of menstrual cycle phase. METHODS: Sixteen healthy women with normal menstrual cycles ingested ethanol at four hormonally distinct phases of the menstrual cycle, namely early follicular, late follicular, mid-luteal, and late-luteal. During each session, they first sampled three small doses of ethanol (0.2 g/kg each) at half-hourly intervals. They completed subjective and behavioral tests before the first dose and after each subsequent dose. After consuming the third beverage, the women were allowed to choose up to three additional doses of ethanol (0.2 g/kg), one every 30 min. RESULTS: Ethanol produced subjective effects typical for this drug (such as stimulant-like effects and euphoria), and it impaired eye movements and psychomotor performance. However, the effects of ethanol did not vary according to menstrual cycle phase, and consumption of ethanol also did not vary across the menstrual cycle. CONCLUSIONS: These results suggest that circulating ovarian hormones, like E and P, have little effect on either the acute subjective and behavioral effects of ethanol, or on ethanol consumption.     

Oral epithelial alkaline phosphatase in various phases of menstrual cycle

We report here on the changes in the Alkaline Phosphatase staining reaction in oral mucosa of women in various phases of menstrual cycle. It appears that the highest reaction for alkaline phosphatase is shown just after ovulation (about 15th-16th day of cycle). It is possible to judge the period of ovulation by taking daily smears and staining them for Alkaline phosphatase.     

Pharmacokinetics and safety of oral eletriptan during different phases of the menstrual cycle in healthy volunteers.

The purpose of this study was to determine the pharmacokinetics and safety of eletriptan in different phases of the menstrual cycle. Female volunteers (n = 16) with a regular menstrual cycle (28 +/- 4 days) received a single oral dose of 80 mg eletriptan during each of the four cycle phases: phase 1 (menses), days 1 to 4; phase 2 (follicular), days 6 to 10; phase 3 (ovulatory), days 11 to 13; and phase 4 (luteal), days 21 to 24. Eletriptan plasma concentrations were determined from serial plasma samples taken during a 24-hourperiod after dosing. Blood pressure, pulse rate, and ECG measurements were performed at baseline, 1 and 24 hours after dosing. No significant differences between phases were observed for maximum plasma concentration (cmax, range of means = 188-234 ng/ml), time to maximum concentration (tmax, range of means = 1.8-2.5 h), or systemic exposure (area under the curve [AUC], range of means = 1194-1514 ng x h/ml). Although there was a statistically significant difference in the terminal phase elimination rate constant (kel) between phases 1 and2 (0.175/h vs. 0.158/h, p = 0.044), the corresponding difference in terminal phase half-life (t 1/2) (4.0 h vs. 4.4 h) was not considered to be clinicallyrelevant. No clinically relevant differences in blood pressure, pulse rate, or ECG were observed, and the incidence, nature, and severity of adverse events were similar in all phases. The different phases of the menstrual cycle had no clinically significant effect on the pharmacokinetics, safety, or tolerability of oral 80 mg eletriptan in healthy females.     

Effects of triazolam at three phases of the menstrual cycle.

This study investigated the subjective and behavioral effects of a commonly used benzodiazepine, triazolam, in healthy women at three phases of the menstrual cycle: follicular, periovulatory, and luteal. Ovarian hormones or their metabolites have direct and indirect actions on neuronal receptors, which may affect responses to psychoactive drugs acting on the same central nervous system receptors. This study explored the effect of menstrual cycle phase on the mood-altering and performance effects of a single oral dose of the benzodiazepine triazolam. Twenty women received triazolam (0.25 mg orally) or placebo at the follicular, periovulatory, and luteal phases of their menstrual cycles in a within-subject design. Dependent measures included self-reported mood states, psychomotor performance, and plasma levels of triazolam, estradiol, progesterone, and allopregnanolone. After administration of triazolam, most subjects reported the expected increases in fatigue and decreases in arousal and psychomotor performance. Neither plasma levels nor mood and performance effects of triazolam differed across the three phases. This study illustrates a useful methodology for assessing responses to psychoactive drugs in normally cycling women and shows that the effects of this drug were highly stable across the cycle.     

Pharmacokinetics of intravenous cocaine across the menstrual cycle in rhesus monkeys.

Several studies in rodents suggest that there are sex differences in response to cocaine that are related to fluctuations in the ovarian hormones of females. Female rhesus monkeys have menstrual cycles that are remarkably similar to human menstrual cycles in both duration and hormonal variations. Therefore, data obtained in monkeys should be an ideal model for assessing the effects of cocaine across the menstrual cycle in humans. The present study assessed the acute effects of intravenous cocaine (0, 0.25, 0.50, and 1.00 mg/kg) in five female rhesus monkeys during four phases of the menstrual cycle: menses, midfollicular, periovulatory, and midluteal. To reduce the effects of stress that can occur from sedation, all animals were trained to enter primate chairs so that repeated blood samples could be obtained in awake animals. Hormone levels for estradiol and progesterone were measured each session before cocaine administration. Cocaine and cocaine metabolite plasma levels were measured at 5, 15, 30, 45, 60, and 90 min after cocaine administration. Similarly, levels of luteinizing hormone (LH) were measured before, 15, 30, 45, 60, and 90 min after cocaine administration. Within 5 min of cocaine administration, cocaine plasma levels peaked and dose-dependent behavioral changes (ie increased motor activity, mydriasis, and refusal of treats) were observed. These effects typically resolved in 15-30 min. There were few differences in the pharmacokinetic profile of cocaine across the menstrual cycle. However, the cocaine metabolites, BZE and EME, did vary across the menstrual cycle, with both being increased in the luteal phase, particularly following the highest dose of cocaine. In addition, unlike previous studies, cocaine did not produce consistent increases in LH levels. Rather, the change in LH levels depended on menstrual cycle phase and cocaine dose. In summary, there is little evidence that the pharmacokinetics of cocaine vary as a function of menstrual cycle phase.     

Patients with premenstrual dysphoric disorder have increased startle response across both cycle phases and lower levels of prepulse inhibition during the late luteal phase of the menstrual cycle.

Patients with premenstrual dysphoric disorder (PMDD) experience their most intense symptoms during the late luteal phase. The aim of the current study was to compare acoustic startle response and prepulse inhibition in PMDD patients and controls during the follicular and late luteal phases of the menstrual cycle. Following two months of prospective daily ratings on the Cyclicity Diagnoser scale, 30 PMDD patients and 30 asymptomatic controls, between the ages of 20 and 46, were included in the study. The eyeblink component of the acoustic startle reflex was assessed using electromyographic measurements of m. orbicularis oculi. Twenty pulse-alone trials (115 dB 40 ms broad-band white noise) and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a 115 dB 40 ms noise burst preceded at a 100 ms interval by 20 ms prepulses that were 72, 74, 78, or 86 dB. PMDD patients had a significantly higher startle response than controls during both phases of the menstrual cycle (p<0.05). PMDD patients exhibited lower levels of prepulse inhibition with 78 dB and 86 dB prepulses compared to control subjects in the luteal (p<0.01) but not in the follicular phase. Whereas control subjects displayed increased PPI during the late luteal phase compared to the follicular phase (p<0.01), PPI magnitude remained unchanged in PMDD patients between cycle phases. Relative to controls, PMDD patients displayed increased startle reactivity across both menstrual cycle phases and deficits in prepulse inhibition of acoustic startle during the late luteal phase. These findings are consistent with an altered response to ovarian steroids among PMDD patients.     

Pharmacokinetics of repeated doses of intravenous cocaine across the menstrual cycle in rhesus monkeys

Numerous studies in rodents suggest that there are sex differences in response to cocaine that are related to fluctuations in the ovarian hormones of females. Given that female rhesus monkeys have menstrual cycles that are remarkably similar to those of humans, they provide an ideal laboratory animal model for assessing the effects of cocaine across the menstrual cycle. The present study assessed the effects of 4 injections of intravenous (i.v.) cocaine (0.00, 0.25 or 0.50 mg/kg), spaced 15 min apart, in 4 female rhesus monkeys. Each monkey was tested with each dose during 4 phases of the menstrual cycle: menses, midfollicular, periovulatory and midluteal. Estradiol and progesterone levels were measured each session before cocaine administration to verify phase of the menstrual cycle. Cocaine and cocaine metabolite levels were measured 5 min after each cocaine dose and 5, 15, 30, 45, 60 and 120 min after the last cocaine dose. Similarly, levels of luteinizing hormone (LH) and prolactin levels were measured before, 5, 15, 30, 45, 60 and 120 min after the last cocaine dose. Cocaine and metabolite levels increased as a function of dose, but there were minimal differences across the menstrual cycle following repeated injections of cocaine. With a few exceptions, LH levels decreased as a function of time within the session, with no differences as a function of cocaine dose. Cocaine produced transient increases in LH levels during the luteal phase, with maximal levels occurring after the second cocaine injection. Lastly, cocaine substantially decreased prolactin levels across all menstrual cycle phases. Taken together, these data indicate that any behavioral differences observed either across the menstrual cycle or between males and females, are probably not related to alterations in the pharmacokinetics of cocaine across the menstrual cycle.     

Acute effects of d-amphetamine during the follicular and luteal phases of the menstrual cycle in women

Rationale: Little is known about the interactions between ovarian hormones across the menstrual cycle and responses to psychoactive drugs in humans. Preclinical studies suggest that ovarian hormones such as estrogen and progesterone have direct and indirect central nervous system actions, and that these hormones can influence behavioral responses to psychoactive drugs. Objectives: In the present study, we assessed the subjective and behavioral effects of d-amphetamine (AMPH; 15 mg orally) at two hormonally distinct phases of the menstrual cycle in women. Methods: Sixteen healthy women received AMPH or placebo capsules during the follicular and mid-luteal phases of their cycle. During the follicular phase, estrogen levels are low initially and then rise while progesterone levels remain low. During the mid-luteal phase, levels of both estrogen and progesterone are relatively high. Dependent measures included self-report questionnaires, physiological measures and plasma hormone levels. Results: Although there were no baseline differences in mood during the follicular or luteal phase, the effects of AMPH were greater during the follicular phase than the luteal phase. During the follicular phase, subjects reported feeling more “High”, “Energetic and Intellectually Efficient”, and “Euphoric” after AMPH than during the luteal phase, and also reported liking and wanting AMPH more. Further analyses showed that during the follicular phase, but not the luteal phase, responses to AMPH were related to levels of estrogen. Higher levels of estrogen were associated with greater AMPH-induced increases in “Euphoria” and “Energy and Intellectual Efficiency”. During the luteal phase, in the presence of both estrogen and progesterone, estrogen levels were not related to the effects of AMPH. Conclusions: These findings suggest that estrogen may enhance the subjective responses to a stimulant drug in women, but that this effect may be masked in the presence of progesterone. Received: 26 August 1998/Final version: 19 February 1999     

The effects of smoked cocaine during the follicular and luteal phases of the menstrual cycle in women

RATIONALE: Few studies have systematically determined whether the response to cocaine in human females is related to hormonal fluctuations at different phases of the menstrual cycle. OBJECTIVES: To investigate the responses to repeated doses of smoked cocaine in women during two phases of the menstrual cycle using a within-subject design. METHODS: Eleven non-treatment seeking female cocaine smokers were administered smoked cocaine during the follicular and mid-luteal phases of the menstrual cycle. The order of menstrual cycle phase was counterbalanced across women and the order of cocaine doses was randomized. During each phase, there were four cocaine administration sessions. During each session, participants could smoke up to six doses of cocaine (either 0, 6, 12, or 25 mg cocaine base, depending on the session) at 14-min intervals. RESULTS: The number of cocaine doses administered did not vary between the follicular and luteal phases. After cocaine administration, heart rate and several ratings - such as "good drug effect", "high", "stimulated", and "drug quality ratings" - were increased more during the follicular phase than the luteal phase, although, for some measures, these effects varied based on the cocaine dose. Further, dysphoric mood during the luteal phase was improved after cocaine administration. CONCLUSIONS: These results indicate that the cardiovascular and subjective effects of repeated doses of smoked cocaine are complex and vary as a function of menstrual cycle phase and cocaine dose.     

Acute effects of d-amphetamine during the early and late follicular phases of the menstrual cycle in women

Recent preclinical evidence indicates that ovarian hormones, such as estrogen and progesterone, may influence the behavioral effects of psychoactive drugs by interacting directly with neurotransmitter systems in the central nervous system. However, few studies have examined the effects of ovarian hormones on subjective or behavioral responses to psychoactive drugs in humans. In the present study, we assessed the subjective and physiological effects of d-amphetamine during the early and late follicular phases of the menstrual cycle. Nineteen healthy, regularly-cycling women participated in four sessions receiving doses of d-amphetamine (AMPH; 15 mg oral) or placebo during the early and late follicular phases of two menstrual cycles. During the early follicular phase levels of both estrogen and progesterone are low, whereas during the late follicular phase estrogen levels are higher while progesterone remains low. Dependent measures included self-report questionnaires, physiological measures and plasma hormone levels. Most of the subjective and physiological effects of AMPH were not affected by menstrual cycle phase. However, subjects reported greater Unpleasant Stimulation after AMPH, and less Unpleasant Sedation, during the late follicular phase than during the early follicular phase. These results provide limited evidence that higher levels of estrogen during the late follicular phase alter the subjective effects of AMPH in normal, healthy women.     

Relationship between variations in estradiol and progesterone levels across the menstrual cycle and human performance

RATIONALE: Studies about whether or not the cognitive performance of women is influenced by changes in levels of sex steroid hormones across the menstrual cycle have produced ambiguous results. OBJECTIVES: This study tested whether flight simulator performance differs significantly between the menstrual and the luteal phase of the menstrual cycle. METHODS: In a within-subjects design, 24 female pilots were tested twice during their menstrual cycle: once during the menstrual and once during the luteal phase. On both test days they performed a 75-min simulator flight in a Frasca 141, a popular pilot training device. RESULTS: Despite highly significant differences in estradiol (E2) as well as progesterone (P) levels on the 2 test days, and despite excluding subjects with anovulatory cycles from the analyses, there were no significant differences in overall flight performance between the menstrual and luteal phases. We found no significant correlations between E2 or P levels and flight performance. CONCLUSIONS: We found no evidence that the tested menstrual cycle phases and their associated E2 and P levels significantly influence flight simulator performance. We consider these negative findings based on 24 subjects meaningful because previous studies on the influence of menstrual cycle on cognitive performance have not involved complex "real world" tasks such as piloting an aircraft and they obtained inconsistent results.     

Changes in food consumption and body weight associated with smoking cessation across menstrual cycle phase

Forty women smokers were randomly assigned to smoking cessation for a 10-day period of time, either during the follicular or the luteal phase of their menstrual cycle. Measurements of dietary intake and body weight were collected during the same phase the previous (smoking as usual) month and during the cessation phase. Physical activity was controlled across the 2 months. Comparisons between the smoking and cessation months indicated that both groups increased their dietary intake during the cessation month, but no interaction occurred between phase and month. That is, women in both groups increased dietary intake to the same degree. All energy nutrients tested (fat, complex carbohydrates, and sugar) increased significantly from baseline to cessation. Conversely, body weight increased by 1.8 kg (4 lb) in the Luteal group, while weight remained stable (0.1 kg change) in the Follicular group.